A key contributing factor to the initiation and escalation of substance use during early adolescence is affiliation with deviant peers, which often arises when socially isolated or rejected youth aggregate and reinforce substance use and other deviant activity in the group (i.e., deviant peer clustering). Even though the field has developed efficacious prevention programs, few have demonstrated strong effects on deviant peer clustering. Further, on a national level, substance use among adolescents continues to be high, suggesting that a fresh approach to prevention with a renewed focus on the peer context is needed to create a broad, sustainable public health impact. This application represents an approach to prevention in which evolutionary theory provides a unifying theoretical framework. This framework implies that diverse problems are due to social environments that are unfavorable for the expression of prosocial behaviors, instead eliciting a variety of self-oriented or exploitative behaviors. Systematic efforts to reduce multiple problems among youth (e.g., substance use, risky sex, depression, academic failure, etc.) need to look beyond the immediate issues to the social conditions that make the entire range of problems more likely. We need prevention programs that can modify key social environments to nurture prosocial behavior and minimize the toxic or stressful conditions that give rise to non- prosocial behaviors in youth. In addition, translating scientific knowledge into a broad public health impact requires that we better understand the etiology and function of prosocial behavior in group settings. We must better understand how relationships, rewards, and behavior can promote greater prosociality across large groups, how prosociality circulates through social networks, how it persists or declines as a function of contextual norms, and how it can suppress problem behavior. In this project, we propose to integrate several simple, flexible, and powerful strategies that have proven value in establishing a social context conducive to positive peer group development. Our goal is to reduce rejection and social isolation, promote new friendships among youth from different social groups, and simultaneously encourage greater levels of prosocial behavior. This should create a positive feedback loop in which the social and behavioral processes amplify one another to bring significant change to the school social context, interrupting the process of deviant peer clustering and addressing a key root cause of escalations in substance use and related problem behavior in adolescence. We will test our approach in a small-scale RCT involving 12 middle schools in Oregon. We will evaluate the main effects of our program on prosocial behavior and substance use and explore links among rejection, prosocial behavior, and substance use over time to determine directionality of effects. We will also use RSiena to evaluate social network processes (e.g., deviant peer clustering, influence vs. selection for prosocial behavior) as mediators of intervention effects. Significant results from our project should promote substantial interest in our approach within schools and districts, creating a broad, organically-driven impact on adolescent health.